The immune response is a highly regulated process with deficient activation being manifested by decreased resistance to infections and probably malignancy and altered, poorly controlled or excessive activation by allergy and autoimmunity. Triggering and modulation of the inflammatory and/or immune response appear to be exerted through specific cell surface receptors for antigens, immunoglobulins, complement and other factors. These receptors on highly purified immunocompetent cells are being investigated in regard to their susceptibility to pharmacologic manipulation, mode of biochemical linkage to the interior of the cell, and physicochemical structure. Utilizing affinity chromatography and immunoprecipitation, isolation and physicochemical characterizaton of the Fc and C3b receptor on immunocompetent cells is being pursued. Phagocytosable particles, sensitized with immunoglobulins and/or complement, are exposed to granulocytes and monocytes (macrophages) so as to engage the receptor under study. In other studies these same cells are challenged with chemotactic factors and other soluble activators. The alteration of cellular metabolism consequent to the attachment and/or investigation of the particles and soluble activating factors is then examined in regards to the role of cyclic nucleotides, protein phosphorylation and cytochalasin binding proteins. In related studies ascorbic acid and ethanol, agents which alter cyclic nucleotide levels, are being studied as to their ability to modulate lymphocyte mitogenesis, histamine release and lysosomal enzyme release. The key objective of these investigations is to obtain a better understanding of the mechanism whereby surface phenomena, consisting of the attachment and in some cases ingestion of immune-complexes and the binding of soluble activating factors to specific receptors occur and then mediate and/or modulate a cellular response.